Direct and indirect effect of IL-17A on platelet aggregation

Fulvio D'Acquisto, Reader in Immunopharmacology,
April 13, 2016

Dear Editor,

A recent report by Hot and colleagues investigated the possible link between the increased expression of IL-17 in rheumatoid diseases and the high incidence of cardiovascular disorders in patients suffering these pathologies.

To address this point the authors used an elegant approach that combined in vitro cell functional studies with gene fingerprint analysis by microarray. Consistent with several previous studies, including our own (1), the authors showed that IL-17A per se does not cause a significant inflammatory response in HUVEC while it greatly enhance the inflammatory properties of TNF?.

To investigate the functional consequences of these results the authors used a wide range of tests including endothelial cell migration and invasion. Most interestingly, they also showed that the conditioned medium of HUVEC stimulated with IL-17A with or without TNF? caused a significant increase in platelet aggregation.

These results further support our previous studies showing a proaggregant effect of IL-17A on both murine and human platelet aggregation (2). Like for endothelial cells, IL-17A alone did not influence platelet activation while it amplified the inflammatory effect of ADP. More specifically, IL-17A increased the primary reversible phase of ADP-induced platelet aggregation in a concentration-dependent manner.

The results presented by Hot et al. in Figure 6A show no difference between the conditioned medium of HUVEC treated with IL-17A or IL-17A + TNF? while in most of the other assays the combination of these two cytokines provided significant differences compared to the effects of IL- 17A alone. Thus it might be possible to hypothesize that the proaggregant effect observed might be due, al least in part, to a direct effect of IL- 17A still present in the medium. This could be easily addressed by adding an anti-IL-17A neutralizing antibody to the conditioned medium before the test on platelet aggregation.

References

1. Maione F, Paschalidis N, Mascolo N, et al. Interleukin 17 sustains rather than induces inflammation. Biochem Pharmacol 2009;77(5):878-87.

2. Maione F, Cicala C, Liverani E, et al. IL -17A increases ADP-induced platelet aggregation. Biochem Biophys Res Commun 2011;408(4):658-62.

Conflict of Interest:

None declared

Conflict of Interest

None declared